1. Field of the Invention
The present invention is concerned with a novel method of preparation for 4-amino-3-hydroxy-2,4-(disubstituted)pentanoic acids having the following configuration: (2S, 3S, 4R).
The pentanoic acids prepared by the novel method of the present invention are useful as intermediates in preparing antibacterial compounds. Particularly, (2S, 3S, 4R)-4-amino-3-hydroxy-2-methylpentanoic acid (AHMPA) is a key element in the synthesis of the antitumor, antibiotic bleomycin A.sub.2, thus making its availability in high enantiomeric purity desirable.
2. Brief Description of the Prior Art
Evans et al., J. Am. Chem. Soc., (1981 103, 2127, and J. Am. Chem. Soc., (1982) 104, 1737, describes enantioselective synthesis of .alpha.-substituted carboxylic acid derivatives utilizing the asymmetric alkylation reactions of chiral imide enolates derived from N-acyl oxazolidones. However, enantioselective acylation is not described, nor are the remaining novel steps of the method of the present invention suggested.
Takita et al., Tetrahedron Lett., (1982) 23, 521, describes the total synthesis of bleomycin A.sub.2, but nowhere suggests the method of the present invention.
Narita et al., Tetrahedron Lett., (1982) 23, 525, describes stereoselective synthesis of (2S, 3S, 4R)-4-amino-3-hydroxy-2-methylpentanoic acid (AHMPA) through aldol condensation of (R)-2-aminopropionaldehyde derivatives and E-vinyloxyboranes; Ohgi and Hecht, J. Org. Chem., (1981) 46, 1232, describes preparation of AHMPA from L-rhamnose as an alternative to the stereoselective aldol condensation; Levin et al., J. Amer. Chem. Soc., (1980) 102 1452, describes obtaining the desired 2S, 3S, 4R configuration by cyclization to the lactam, epimerization, hydrolysis, and fractional crystallization; and Yoshioka et al., J. Antibiotics, (1974) 27, 356 describes a biosynthetic-like synthesis of (2S, 3S, 4R)-4-amino-3-hydroxy-2-methyl-n-valeric acid. However, none of the above references suggests the method of the present invention.